The Impact of Heart Rate on Central Blood Pressure in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker

The Impact of Heart Rate on Central Hemodynamics in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker

This study is divided into two parts:

• The first part evaluates the acute effect of non-pharmacological heart rate change on central hemodynamic parameters noninvasively in sick sinus syndrome patients with a permanent cardiac pacemaker
• The second part evaluates the acute effects of atenolol, nebivolol and ivabradine on central hemodynamic parameters noninvasively in sick sinus syndrome patients with a permanent cardiac pacemaker at different pacing rate levels

Study Overview

• Status: Completed
• Conditions: Aortic Blood Pressure
• Intervention / Treatment: Device: AAI 40 bpm; Device: AAI 60 bpm; Device: AAI 90 bpm; Drug: Atenolol Pill; Drug: Nebivolol Pill; Drug: Ivabradine Pill

Detailed Description

Patients with sick sinus syndrome and a double-chamber cardiac pacemaker are studied.

• To investigate the role of non-pharmacological heart rate change on central hemodynamics in the first part of the study, the investigators acutely change pacing rate from atrial paced-atrial sensed (AAI)-mode 60 to 40 to 90 bpm and obtain hemodynamic parameters noninvasively after a short stabilisation period after each pacemaker rate change.
• Subsequently, to investigate the acute effects of beta-blockers or ivabradine on central hemodynamics in the second part of the study, the investigators obtain central hemodynamic parameters noninvasively after acute administration of atenolol, nebivolol or ivabradine at the same pacing rate levels used in the first part of the study (AAI-mode 60, 40 and 90 bpm).

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-75 years;
• dual-chamber pacemaker implanted due to sick sinus syndrome at least six months before; sinus rhythm

Exclusion Criteria:

• average seated office brachial systolic BP ≥160 mmHg and/or diastolic BP ≥ 100 mmHg; atrial pacing <40%;
• ventricular pacing >25%;
• unpaced QRS >120 ms and/or QTc >500 ms on 12-lead ECG;
• atrioventricular blockage at AAI-mode 90 bpm; resting HR >60 bpm at AAI-mode 40 bpm; irregular heart rate;
• automatic mode switching >10%;
• implantable cardioverter defibrillator or cardiac resynchronisation therapy pacemaker; treatment with digoxin, class Ic or III antiarrhythmic drugs;
• history of acute coronary syndrome;
• stable angina pectoris;
• heart failure with reduced left ventricular ejection fraction;
• history of cerebrovascular event;
• diabetes mellitus;
• chronic kidney disease with eGFR <30 ml/min/m2;
• peripheral artery disease;
• clinically relevant heart valve disease;
• active cancer;
• acute or chronic inflammatory disease;
• severe chronic respiratory or liver disease;
• pregnancy or breastfeeding
• contraindication or intolerance to atenolol, nebivolol, ivabradine or adjuvants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Subjects; Subjects with a cardiac pacemaker

Device: AAI 40 bpm; Cardiac pacemaker of the subjects is set to AAI-mode 40 bpm in the first and second part of the study; Device: AAI 60 bpm; Cardiac pacemaker of the subjects is set to AAI-mode 60 bpm in the first and second part of the study; Device: AAI 90 bpm; Cardiac pacemaker of the subjects is set to AAI-mode 90 bpm in the first and second part of the study; Drug: Atenolol Pill; 50 or 100 mg of atenolol is administered to subjects in the second part of the study; Drug: Nebivolol Pill; 5 mg of nebivolol is administered to subjects in the second part of the study; Drug: Ivabradine Pill; 5 or 7,5 mg of ivabradine is administered to subjects in the second part of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First part of the study: central systolic blood pressure		3 minutes after heart rate change
Second part of the study: systolic blood pressure amplification	difference between peripheral and central systolic blood pressure	3 hours after drug administration and 3 minutes after heart rate change

Collaborators and Investigators

• Sponsor: Tartu University Hospital

Publications and helpful links

General Publications

• Teeaar T, Serg M, Paapstel K, Vahi M, Kals J, Cockcroft JR, Zilmer M, Eha J, Kampus P. Atenolol's Inferior Ability to Reduce Central vs Peripheral Blood Pressure Can Be Explained by the Combination of Its Heart Rate-Dependent and Heart Rate-Independent Effects. Int J Hypertens. 2020 Apr 26;2020:4259187. doi: 10.1155/2020/4259187. eCollection 2020.
• Teeaar T, Serg M, Paapstel K, Kals J, Kals M, Zilmer M, Eha J, Kampus P. Heart rate reduction decreases central blood pressure in sick sinus syndrome patients with a permanent cardiac pacemaker. J Hum Hypertens. 2018 May;32(5):377-384. doi: 10.1038/s41371-018-0051-4. Epub 2018 Mar 27.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: August 8, 2017
• First Submitted That Met QC Criteria: August 9, 2017
• First Posted (Actual): August 10, 2017

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: ivabradine; heart rate; beta-blockers; sick sinus syndrome; aortic blood pressure; artificial pacemaker
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Arrhythmia, Sinus; Heart Block; Sick Sinus Syndrome; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Atenolol
• Other Study ID Numbers: 14058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all data shared after completion of study as supplement to journal article

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No